Adenylate cyclases in vertebrate retina: enzymatic characteristics in normal and dystrophic mouse retina.
Adenylate cyclase activity and the effects of various activators and inhibitors of this enzyme were measured in retinas from normal mice (C57BL/6J) and congenic animals with photoreceptor dystrophy. In normal retina, approximately 250 microM-ATP was required for half-maximal stimulation of the enzyme. Activity was supported by Mg2+ and Mn2+, but Ca2+ was ineffective. The enzyme was inhibited by EGTA and stimulated by 5'-guanylylimidodiphosphate (GPP(NH)P), dopamine, and NaF. The stimulatory effects of GPP(NH)P and dopamine were greater in the presence of EGTA. Examination of microdissected normal retinas revealed that the inner (neural) retina had adenylate cyclase activity four times that of the photoreceptor cell layers, and that EGTA inhibited activity in the inner retina, but had no effect in the outer retina. In dystrophic retinas basal enzyme activity was 60% higher than that in normal retina. The enzyme in this tissue was stimulated by EGTA, GPP(NH)P, and dopamine, and their effects were additive. These results indicate that adenylate cyclase activity in vertebrate retina is under complex regulation by substrate, divalent cations, guanine nucleotides, dopamine, and perhaps calmodulin. In addition, the data demonstrate that adenylate cyclase is not evenly distributed in the retina and that it is regulated differently in the inner and outer retina. Finally, the present results indicate that regulation of this enzyme in dystrophic retina may be qualitatively and quantitatively different from that in normal retina.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008345:Manganese / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009137:Muscular Dystrophy, Animal / Q000201:enzymology*; D012160:Retina / Q000201:enzymology*
D006165:Guanylyl Imidodiphosphate; D008345:Manganese; D004533:Egtazic Acid; D000262:Adenylyl Cyclases; D008274:Magnesium; D002118:Calcium; D004298:Dopamine